1-Ethyl-3-(5-nitrothiazol-2-yl) harnstoff

Crystals

Solid

less than 1 mg/mL at 73 °F (NTP, 1992)

Orange plates; solubility in water: 8 g/100 ml; aqueous soln are alkaline and unstable /Sodium salt/

Crystals; solubility in water: 3 g/100 ml; aqueous soln are more stable than those of sodium salts /Potassium salt/

In water, 30 mg/l @ 25 °C

442 °F (decomposes) (NTP, 1992)

Decomposes @ 228 °C

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 670(SRC), determined from a water solubility of 30 mg/l(2) and a regression-derived equation(3), indicates that nithiazide is expected to have low mobility in soil(SRC). The pKa of nithiazide is 7.3(2), indicating that this compound will partially exist in cation form in the environment; cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(4). Volatilization of nithiazide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-15 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Nithiazide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-7 mm Hg(SRC), determined from a fragment constant method(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 670(SRC), determined from a water solubility of 30 mg/l(2) and a regression-derived equation(3), indicates that nithiazide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.6X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The pKa of nithiazide is 7.3(2), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(5). According to a classification scheme(6), an estimated BCF of 90(SRC), from its water solubility(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), nithiazide, which has an estimated vapor pressure of 1.3X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere(SRC). Vapor-phase nithiazide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.1 days(SRC), calculated from its estimated rate constant of 5.2X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=139-94-6]

The Koc of nithiazide is estimated as 670(SRC), using water solubility of 30 mg/l(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that nithiazide is expected to have low mobility in soil(SRC). The pKa of nithiazide is 7.3(1), indicating that this compound will partially exist in cation form in the environment; cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(4).

Nithiazide

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 31: (1983) Some Food Additives, Feed Additives and Naturally Occurring Substances

1987

1987

Nithiazide

An estimated BCF of 90 was calculated for nithiazide(SRC), using a water solubility of 30 mg/l(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Henry's Law constant for nithiazide is estimated as 1.6X10-15 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that nithiazide is expected to be essentially nonvolatile(SRC). Nithiazide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-7 mm Hg(SRC), determined from a fragment constant method(2).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 50 male and 50 female B6C3F1 mice, six weeks of age, were fed diets containing 2500 or 5000 mg/kg nithiazide (purity unspecified) for 61 weeks, then control diet for nine weeks (due to a shortage of nithiazide), then nithiazide diets for 33 weeks, then control diet for one week - providing a total /study/ ... period of 104 weeks. ...A group of 20 mice of each sex served as matched controls. Mean body weight gain of treated male and female mice was distinctly reduced. /No effect on mortality was noted./... Statistically significant (p=0.002), dose-related increased incidences of hepatocellular carcinomas or adenomas were observed in male mice: controls, 4/20 (2 carcinomas); low-dose, 15/46 (6 carcinomas); high-dose, 25/43 (12 carcinomas) (p=0.005).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 50 male and 50 female Fischer 344 rats, 6 weeks of age, were fed diets containing 625 or 1250 mg/kg nithiazide (purity unspecified) for 38 weeks, then control diet for 9 weeks (due to shortage of nithiazide), then nithiazide diets for 56 weeks, then control diet for 1 wk - providing a total observation period of 104 weeks. The doses were selected on the basis of a range-finding study. A group of 20 rats of each sex served as matched controls. Mean body weight gain of treated male and female rats was slightly reduced. No significant dose-related trend in mortality was seen for either sex: by the end of the study, 80, 64 and 66% of males and 85, 66 and 84% of females were still alive in the control, low-dose and high-dose groups, respectively. Statistically significant (p=0.003) dose-related increased incidences of fibroadenomas or cystadenomas of skin, subcutaneous tissue and mammary gland were observed in female rats: controls, 1/20; low-dose, 5/50; high-dose 15/50 (p=0.020); and statistically significant dose-related increased incidences of chromophobe adenomas or acidophil adenomas of the pituitary (p=0.034): controls, 5/18; low-dose, 13/39; high-dose, 24/47; and of endometrial stromal polyps of the uterus (p=0.039): controls, 1/19; low-dose, 4/50; high-dose, 10/50, were also observed. No statistically significantly increased incidence of tumors was seen in treated male rats when compared with controls.

Classification of carcinogenicity: 1) evidence in humans: no data; 2) evidence in animals: limited. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent is not classifiable as to its carcinogenicity to humans. /From table/

The rate constant for the vapor-phase reaction of nithiazide with photochemically-produced hydroxyl radicals has been estimated as 5.2X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.1 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Nithiazide is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2) nor to directly photolyze due to the lack of absorption in the environmental UV spectrum (>290 nm)(SRC).

Nithiazide's production and use as a veterinary medicine may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.3X10-7 mm Hg at 25 °C indicates nithiazide will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase nithiazide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 3.1 days. Particulate-phase nithiazide will be removed from the atmosphere by wet and dry deposition. If released to soil, nithiazide is expected to have low mobility based upon an estimated Koc of 670. The pKa of nithiazide is 7.3, indicating that this compound will partially exist in cation form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.6X10-15 atm-cu m/mole. If released into water, nithiazide is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 90 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to nithiazide may occur by dermal contact with this compound at workplaces where nithiazide is produced or used. (SRC)

Prepd by the condensation of ethyl isocyanate with 2-amino-5-nitrothiazole in toluene.

O'Neill et al., US 2755285 (1956 to Merck & Co.)